KSRP-mediated Wnt/β-catenin activation promotes follicular thyroid cancer progression and stemness

K-homology-type splicing regulatory protein (KSRP) is an RNA-binding protein involved in mRNA decay and translational repression through recognition of adenine-uracil-rich elements. Although KSRP regulates approximately 16% of transcript expression, its role in cancer remains poorly defined.

KSRP expression was analysed using qPCR, Western blot, and immunohistochemistry. Its functional role in follicular thyroid cancer (FTC) was examined through in vitro and in vivo assays. Luciferase reporter and rescue experiments were performed to elucidate the underlying molecular mechanisms.

KSRP was significantly upregulated in FTC tissues and metastatic cell lines. Functional studies demonstrated that KSRP enhances the invasiveness and stemness of FTC cells. Mechanistically, KSRP promotes nuclear accumulation and transcriptional activity of β-catenin by downregulating the Wnt inhibitors DACT2 and SFRP2.

This study identifies KSRP as an oncogenic factor in FTC that activates Wnt/β-catenin signalling, suggesting its potential as a therapeutic target for FTC patients.